early brain dysfunction that could be assessed as an outcome measure in response to therapeutic interventions. very mildly impaired humans who are developing AD pathology, the sleep-wake cycle may be a useful indicator of accumulation. If analogous abnormalities in the sleep-wake cycle are present in cognitively normal and β caused by A fluctuation and normal sleep patterns. These findings sugg...

The membrane bound metalloprotease meprin β is important for collagen fibril assembly in connective tissue formation and for the detachment of the intestinal mucus layer for proper barrier function. Recent proteomic studies revealed dozens of putative new substrates of meprin β, including the amyloid precursor protein (APP). It was shown that APP is cleaved by meprin β in distinct ways, either ...

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clini...

Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β (Aβ) peptide represents an important molecular target for intervention in Alzheimer's disease. Several types of Aβ peptide immunotherapy for Alzheimer's disease are under investigation, direct immunization with synthetic inta...

Alzheimer's disease (AD) is the most common neurodegenerative disease. Imbalance between the production and clearance of amyloid β (Aβ) peptides is considered to be the primary mechanism of AD pathogenesis. This amyloid hypothesis is supported by the recent success of the human anti-amyloid antibody aducanumab, in clearing plaque and slowing clinical impairment in prodromal or mild patients in ...

A major neuropathological hallmark of Alzheimer's disease is the deposition of amyloid plaques in the brains of affected individuals. Amyloid plaques mainly consist of fibrillar β-amyloid, which is a cleavage product of the amyloid precursor protein. The amyloid-cascade-hypothesis postulates Aβ accumulation as the central event in initiating a toxic cascade leading to Alzheimer's disease pathol...

A detailed analysis of the NMR spectra of amyloid-β (Aβ) peptide revealed a decrease in signal intensity at higher temperature, due to a reversible conformational change of the molecule. Although peak intensity did not depend on peptide concentrations, the intensity in the region from D23 to A30 depended significantly on temperature. During the early stages of Aβ aggregation, each molecule migh...

Some of the lysozyme mutants in humans cause systemic amyloidosis. Hen egg white lysozyme (HEWL) has been well studied as a model protein of amyloid fibrils formation. We previously identified an amyloid core region consisting of nine amino acids (designated as the K peptide), which is present at 54-62 in HEWL. The K peptide, with tryptophan at its C- terminus, has the ability of self-aggregati...

Aβ amyloid fibrils, which are related to Alzheimer's disease, have a cross-β structure consisting of two β-sheets: β1 and β2. The Aβ peptides are thought to be serially arranged in the same molecular conformation along the fibril axis. However, to understand the amyloid extension mechanism, we must understand the amyloid fibril structure and fluctuation at the fibril end, which has not been rev...